Dry eye is an ophthalmic condition characterized by a discontinuous tear film of the ocular surface. The condition has a number of distinct etiologies, including poor water-secretion by the lacrimal gland (Sjogren), poor mucin secretion by the goblet cells (Lemp), vitamin A deficiency (Lawrence), and alteration of film-forming lipids as a result of chronic bletharitis.
Dry eye is usually treated by applying a slightly viscous polymer solution in drop form to the eye, to provide temporary wetting before the solution evaporates or is wiped away by blinking. Since the polymer solutions tend to be cleared from the eye rather quickly, frequent dosing may be required.
The usual dry eye formulation is a liquid which is intended to be stored at room temperature. For this reason, it is desirable that the product be stable on storage at room temperature over a several-month period. For polymer solutions of the type just described, the principal storage problem is bacterial growth, which can be controlled by the presence of a bacteriostatic compound. One bacteriostatic compound which has been widely used is benzalkonium chloride, at a solution concentration of about 0.01%. Although generally safe for ophthalmic use, the compound has been found to cause occasional eye irritation.
The inventors have previously proposed, in co-owned patent application for "Ophthalmic Liposomes", Ser. No. 890,817 filed June 19, 1986, the use of liposome suspensions for treating dry eye. This method of treatment provides several potential advantages over prior art treatment involving polymer solutions. Liposomes, when bound to the ocular surface, would provide a matrix for holding encapsulated and bound aqueous fluid, and thus could provide effective wetting as long as the liposomes are retained on the ocular surface. The liposomes can also provide muco-mimetic properties for forming a stable tear film on the eye. According to the earlier-described invention, and also to the invention disclosed herein, the liposomes can be formulated for retention on the ocular surface for up to several hours, and thus the need for frequent dosing is avoided. Further, the liposomes can be formulated to supply film-forming lipids and/or vitamin A which may be lacking in the patient receiving the treatment.
Although liposomes offer the potential for improved dry eye treatment, there are several challenges in the design of an effective dry eye formulation. One is that the product be stable for periods of up to several months. It is well-known that liposomes undergo a variety of lipid oxidation/peroxidation and hydrolysis reactions, even when stored at refrigerator temperature for several months. Another problem is achieving good optical clarity in the formulation, so that the liposomes do not impair or cloud vision. Finally, the liposome suspension must be compatible with an acceptable bacteriostatic agent.